Pharmacokinetics of Single-Dose Oral Ranolazine in Hemodialysis Patients

Phase 4

Completed

• Conditions: End-stage Renal Disease; Cardiovascular Disease
• Interventions: Drug: Ranolazine; Procedure: Pharmacokinetic Blood and Dialysate Sampling; Procedure: QT Interval

• Registration Number: NCT01435174
• Lead Sponsor: University of Michigan

Brief Summary

End-stage renal disease (ESRD) patients often develop cardiovascular complications, and cardiovascular disease is the leading cause of death in this population. Ranolazine's ability to treat angina without reducing heart rate or blood pressure makes it an important option for ESRD patients. The hemodialysis clearance of ranolazine is unknown. A single-dose pharmacokinetic study is needed to characterize ranolazine and its metabolites in ESRD patients on and off hemodialysis. Results of the proposed study will provide initial dosing estimates for a follow-up, multiple-dose pharmacokinetic study in this population.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-09-14
• Study First Submitted QC: 2011-09-14
• Study First Posted: 2011-09-16
• Study Start: 2011-10
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Results First Submitted: 2014-05-21
• Results First Submitted QC: 2014-05-21
• Results First Posted: 2014-06-25
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-13
• Last Update Posted: 2017-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

• 18-74 years of age
• Within 50% of ideal body weight and greater than 40 kg
• Chronic kidney disease (CKD) stage 5 receiving maintenance hemodialysis for at least 3 months
• Native kidney estimated glomerular filtration rate(GFR) < 10 mL/min
• No concurrent illness or evidence of infection
• Able to give informed consent

Exclusion Criteria

• QTc interval > 470 msec at echocardiogram (ECG) obtained within the last 6 months
• Concomitant QT-prolonging drugs, major P-gp inhibitors, and CYP3A4 inducers and inhibitors including: cyclosporine, rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's Wort, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir, quinidine, dofetilide, sotalol, amiodarone, erythromycin, thioridazine, ziprasidone, haloperidol, trimethoprim/sulfamethoxazole, ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin
• Pre-study hemoglobin < 9.5 g/dL
• Plasma albumin < 2.5 g/dL
• Liver disease - exclude subjects with a Child Pugh score of C or higher
• Positive pregnancy test
• Breastfeeding
• Allergy to ranolazine
• Participating in another investigational study
• Hepatitis B infection due to dialysis isolation requirements
• Unstable blood pressure control
• Need for routine large fluid removal during dialysis (> 4L)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ranolazine	Pharmacokinetic Blood and Dialysate Sampling	End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.
Ranolazine	QT Interval	End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.
Ranolazine	Ranolazine	End-stage renal disease patients receiving a single-dose of ranolazine and a concomitant hemodialysis session.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameters of Ranolazine	At hours post-dose: 0, 2, 4, 8, 12, 15, 18, 20, 22, 23, 26, 30, 65	Peak Plasma Concentration (Cmax) with a 500 mg dose of ranolazine

Trial Locations

Locations (1)

University of Michigan Hospital; 🇺🇸 Ann Arbor, Michigan, United States